PMID- 34046037
OWN - NLM
STAT- MEDLINE
DCOM- 20211101
LR  - 20211101
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 12
DP  - 2021
TI  - Identification of Potentially Therapeutic Immunogenic Peptides From 
      Paracoccidioides lutzii Species.
PG  - 670992
LID - 10.3389/fimmu.2021.670992 [doi]
LID - 670992
AB  - Paracoccidioidomycosis (PCM) is an endemic mycosis in Latin America caused by the 
      thermodimorphic fungi of the genus Paracoccidioides spp. Paracoccidioides lutzii 
      (PL) is one of the 5 species that constitute the Paracoccidioides genus. PL 
      expresses low amounts of glycoprotein (Gp) 43 (PLGp43) and PLGp43 displays few 
      epitopes in common with the P. brasiliensis (PB) immunodominant antigen PBGp43, 
      which is commonly used for serological diagnosis of PCM. This difference in 
      structure between the glycoproteins markedly reduces the efficiency of 
      serological diagnosis in patients infected with PL. We previously demonstrated 
      that peptide 10 (P10) from the PBGp43 induces protective immune responses in in 
      vitro and in vivo models of PB PCM. Since, P10 has proven to be a promising 
      therapeutic to combat PB, we sought to identify peptides in PL that could 
      similarly be applied for the treatment of PCM. PL yeast cell proteins were 
      isolated from PL: dendritic cell co-cultures and subjected to immunoproteomics. 
      This approach identified 18 PL peptides that demonstrated in silico predictions 
      for immunogenicity. Eight of the most promising peptides were synthesized and 
      applied to lymphocytes obtained from peptide-immunized or PL-infected mice as 
      well as to in vitro cultures with peptides or dendritic cells pulsed the 
      peptides. The peptides LBR5, LBR6 and LBR8 efficiently promoted CD4(+) and CD8(+) 
      T cell proliferation and dendritic cells pulsed with LBR1, LBR3, LBR7 or LBR8 
      stimulated CD4(+) T cell proliferation. We observed increases of IFN-gamma in the 
      supernatants from primed T cells for the conditions with peptides without or with 
      dendritic cells, although IL-2 levels only increased in response to LBR8. These 
      novel immunogenic peptides derived from PL will be employed to develop new 
      peptide vaccine approaches and the proteins from which they are derived can be 
      used to develop new diagnostic assays for PL and possibly other Paracoccidioides 
      spp. These findings identify and characterize new peptides with a promising 
      therapeutic profile for future against this important neglected systemic mycosis.
CI  - Copyright (c) 2021 Silva, Taira, Cleare, Martins, Junqueira, Nosanchuk and Taborda.
FAU - Silva, Leandro B R
AU  - Silva LBR
AD  - Departamento de Microbiologia, Instituto de Ciencias Biomedicas, Universidade de 
      Sao Paulo, Sao Paulo, Brazil.
AD  - Departments of Medicine (Division of Infectious Diseases) and Microbiology and 
      Immunology, Albert Einstein College of Medicine, New York, NY, United States.
FAU - Taira, Cleison L
AU  - Taira CL
AD  - Departamento de Microbiologia, Instituto de Ciencias Biomedicas, Universidade de 
      Sao Paulo, Sao Paulo, Brazil.
FAU - Cleare, Levi G
AU  - Cleare LG
AD  - Departments of Medicine (Division of Infectious Diseases) and Microbiology and 
      Immunology, Albert Einstein College of Medicine, New York, NY, United States.
FAU - Martins, Michele
AU  - Martins M
AD  - Proteomics Unit, Department of Biochemistry, Chemistry Institute, Federal 
      University of Rio de Janeiro, Rio de Janeiro, Brazil.
FAU - Junqueira, Magno
AU  - Junqueira M
AD  - Proteomics Unit, Department of Biochemistry, Chemistry Institute, Federal 
      University of Rio de Janeiro, Rio de Janeiro, Brazil.
FAU - Nosanchuk, Joshua D
AU  - Nosanchuk JD
AD  - Departments of Medicine (Division of Infectious Diseases) and Microbiology and 
      Immunology, Albert Einstein College of Medicine, New York, NY, United States.
FAU - Taborda, Carlos P
AU  - Taborda CP
AD  - Departamento de Microbiologia, Instituto de Ciencias Biomedicas, Universidade de 
      Sao Paulo, Sao Paulo, Brazil.
AD  - Laboratorio de Micologia Medica (LIM53), Departamento de Dermatologia, Faculdade 
      de Medicina, Instituto de Medicina Tropical de Sao Paulo, Universidade de Sao 
      Paulo, Sao Paulo, Brazil.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210511
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (43 kDa protein, Paracoccidioides)
RN  - 0 (Antigens, Fungal)
RN  - 0 (Fungal Proteins)
RN  - 0 (Peptides)
RN  - Paracoccidioides lutzii
SB  - IM
MH  - Animals
MH  - Antigens, Fungal/genetics/*metabolism
MH  - CD4-Positive T-Lymphocytes/*immunology
MH  - Cell Proliferation
MH  - Cells, Cultured
MH  - Dendritic Cells/*immunology
MH  - Disease Resistance
MH  - Fungal Proteins/genetics/*metabolism
MH  - Humans
MH  - Immunotherapy/*methods
MH  - Lymphocyte Activation
MH  - Macrophage Activation
MH  - Macrophages/*immunology
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Paracoccidioides/*physiology
MH  - Paracoccidioidomycosis/*immunology/therapy
MH  - Peptides/genetics/metabolism
PMC - PMC8144467
OTO - NOTNLM
OT  - PCM
OT  - Paracoccidioides lutzii
OT  - paracoccidioidomycosis
OT  - peptide
OT  - vaccine
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/05/29 06:00
MHDA- 2021/11/03 06:00
PMCR- 2021/01/01
CRDT- 2021/05/28 07:24
PHST- 2021/02/22 00:00 [received]
PHST- 2021/04/26 00:00 [accepted]
PHST- 2021/05/28 07:24 [entrez]
PHST- 2021/05/29 06:00 [pubmed]
PHST- 2021/11/03 06:00 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2021.670992 [doi]
PST - epublish
SO  - Front Immunol. 2021 May 11;12:670992. doi: 10.3389/fimmu.2021.670992. eCollection 
      2021.